Cardiac glycoside induces cell death via FasL by activating calcineurin and NF-AT, but apoptosis initially proceeds through activation of caspases

Pongali B. Raghavendra, Yashin Sreenivasan, Govindarajan T. Ramesh, Sunil K. Manna

    Research output: Contribution to journalArticle

    44 Citations (Scopus)

    Abstract

    Decrease in caspase activity is a common phenomenon in drug resistance. For effective therapeutic intervention, detection of such agents, which affects other pathway independent of caspases to promote cell death, might be important. Oleandrin, a polyphenolic glycoside induced cell death through activation of caspases in a variety of human tumour cells. In this report we provide evidence that besides caspases activation, oleandrin interacts with plasma membrane, changes fluidity of the membrane, disrupts Na+/K+-ATPase pump, enhances intracellular free Ca2+ and thereby activates calcineurin. Calcineurin, in turns, activates nuclear transcription factor NF-AT and its dependent genes such as FasL, which induces cell death as a late response of oleandrin. Cell death at early stages is mediated by caspases where inhibitors partially protected oleandrin-mediated cell death in vector-transfected cells, but almost completely in Bcl-xL-overexpressed cells. Overall, our data suggest that oleandrin might be important therapeutic molecule in case of tumors where cell death pathway occurs due to deregulation of caspase-mediated pathway.

    Original languageEnglish
    Pages (from-to)307-318
    Number of pages12
    JournalApoptosis
    Volume12
    Issue number2
    DOIs
    Publication statusPublished - 02-2007

    All Science Journal Classification (ASJC) codes

    • Pharmacology
    • Pharmaceutical Science
    • Clinical Biochemistry
    • Cell Biology
    • Biochemistry, medical
    • Cancer Research

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